Nitric oxide synthase in rat neuromuscular junctions and in nerve terminals of Torpedo electric organ: its role as regulator of acetylcholine release.
The distribution of nitric oxide synthase on peripheral motor system was studied using a specific antibody against the neuronal isoform of nitric oxide synthase (nNOS). The immunoreactivity for nNOS was detected on the sarcolemmal surface of muscle cells, in intramuscular axons and in neuromuscular synapses. At the neuromuscular junctions, ultrastructural immunolabeling demonstrated that nNOS immunoreactivity was localized mainly into the presynaptic nerve terminals as well as adjacent postsynaptic muscle membrane. Similar immunostaining pattern was present in frog muscles and Torpedo electric organs. After chronic muscle denervation, nNOS immunoreactity at endplate level decreased during the first week but it was upregulated after 30 days of denervation. In denervated endplates, nNOS immunoreactivity was localized in the terminal Schwann cells covering the degenerated neuromuscular junctions whereas nNOS was not detected in Schwann cells under normal conditions. In Torpedo synaptosomes, acetylcholine (ACh) release elicited by potassium depolarization was inhibited by NO donors such as sodium nitroprusside. In contrast, application of inhibitors of NOS activity, aminoguanidine (AMG) and N(omega)-Nitro-L-arginine methyl esther (L-NAME) increased acetylcholine release. These results indicate that nNOS is present at the motor nerve terminals in a variety of vertebrates and that it may be involved in the physiological modulation of ACh release and in the regulation of muscle response to nerve injury.
Ribera
J
J
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Catalonia, Spain.
Marsal
J
J
Casanovas
A
A
Hukkanen
M
M
Tarabal
O
O
Esquerda
J E
JE
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004557:Electric Organ / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000201:enzymology; D009411:Nerve Endings / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism; D014101:Torpedo / Q000502:physiology*
D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D000109:Acetylcholine